Palmitoylethanolamide (PEA)

Pain Therapy

Pain is a very difficult and often chronic condition. Its source can be unknown, making diagnosis and treatment in some situations very difficult. Patients which suffer chronic pain may  need to try a wide range of treatments, both medication and allied health, in an attempt to get the pain under control.

Presentation of Product

Palmitoylethanolamide (PEA) is encapsulated into 200mg or 400mg vegetable based capsules.

Currently this product is available only from compounding pharmacies in Australia and we recommend that you see your doctor to ensure they correctly access your needs and review the available information.

Mode of Action

The main target of PEA is thought to be the peroxisome proliferator-activated receptor alpha (PPAR). (2) This receptor is a regulator of gene networks which control pain and inflammation (3), probably by switching off the nuclear factor-kappaB signaling cascade, (2–5) a key element in the
transcription of genes for proinflammatory mediators (cytokine, chemokines, nitric oxide). PEA also has affinity to cannabinoid-like G protein-coupled receptors GPR55 and GPR119. (6) PEA can influence ion channels (eg, potassium channels) that play a role in pain. (7) Furthermore, PEA might desensitize transient receptor potential cation channel subfamily V member (1) channels on sensory neurons. (8,9)

Pain Treatment

Anti-inflammatory actions allowing for a reduction of peripheral and central sensitization are mediated via both neuronal and nonneuronal cells. The latter comprise glia (in particular microglia, which are the brain’s macrophages) as well as peripheral and central mast cells. (10–13). This profile of may thus explain its broad potential in treating many different disorders related to pain and inflammation. (14)


If you would like to learn more about PEA (Palmitoylethanolamide) please contact our Pharmacists on 1300731755 or email.

PEA is available without a prescription but we recommend that you consult with your Doctor first before commencing therapy.

Please CLICK HERE to download the full PEA study.


  1. Loeser Five crises in pain management. Pain Clin Updates. 2012;20: 1–4.
  2. Lo Verme J, Fu J, Astarita G, et al. The nuclear receptor peroxisome proliferator-activated receptor-alpha mediates the anti-inflammatory actions of palmitoylethanolamide. Mol Pharmacol. 2005;67:15–19.
  3. Darmani NA, Izzo AA, Degenhardt B, et al. Involvement of the can- nabimimetic compound, N-palmitoylethanolamine, in inflammatory and neuropathic conditions. A review of the available preclinical data and first human studies. Neuropharmacology. 2005;48:1154–1163.
  4. Genovese T, Esposito E, Mazzon E, et al. Effects of palmitoylethano- lamide on signaling pathways implicated in the development of spinal cord injury. J Pharmacol Exp Ther. 2008;326:12–23.
  5. Naderi N, Majidi M, Mousavi Z, Khoramian Tusi S, Mansouri Z. The interaction between intrathecal administration of low doses of palmi- toylethanolamide and AM251 in formalin-induced pain related behavior and spinal cord IL1-b expression in rats. Neurochem Res. 2012;37: 778–785.
  6. Yoshihara S, Morimoto H, Ohori M, Yamada Y, Abe T, Arisaka Cannabinoid receptor agonists inhibit Ca(2+) influx to synaptosomes from rat brain. Pharmacology. 2006;76:157–162.
  7. Ho WS, Barrett DA, Randall ‘Entourage’ effects of N-palmitoylethanolamide and N-oleoylethanolamide on vasorelaxation to anandamide occur through TRPV1 receptors. Br J Pharmacol. 2008;6: 837–846.
  8. Appendino G, Ligresti A, Minassi A, et al. Conformationally con- strained fatty acid ethanolamides as cannabinoid and vanilloid receptor probes. J Med Chem. 2009;52:3001–3009.
  9. Loría F, Petrosino S, Mestre L, et al. Study of the regulation of the endocannabinoid system in a virus model of multiple sclerosis reveals a therapeutic effect of Eur J Neurosci. 2008;28: 633–641.
  10. Esposito E, Paterniti I, Mazzon E, et al. Effects of palmitoylethanol- amide on release of mast cell peptidases and neurotrophic factors after spinal cord injury. Brain Behav Immun. 2011;25:1099–1112.
  11. Cerrato S, Brazis P, della Valle MF, Miolo A, Puigdemont A. Effects of palmitoylethanolamide on immunologically induced histamine, PGD2 and TNF-alpha release from canine skin mast Vet Immunol Immunopathol. 2010;133:9–15.
  12. De Filippis D, Luongo L, Cipriano M, et al. Palmitoylethanolamide reduces granuloma-induced hyperalgesia by modulation of mast cell activation in rats. Mol Pain. 2010;10:7:3
  13. Keppel Hesselink Glia as a new target for neuropathic pain, clinical proof of concept for palmitoylethanolamide, a glia modulator. Anesth Pain Intensive Care. 2011;15:143–145.
  14. Desio Combination of pregabalin and palmitoylethanolamide (PEA) for neuropathic pain treatment. Pathos. 2010;17:9–14.

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